An effective prophylactic vaccine for HIV-1 may have to elicit multiple immune responses, such as neutralizing antibodies and cytotoxic T-lymphocytes (CTL). However, it had not been formally tested whether the induction of antibodies alone are sufficient to prevent disease. We previously reported the sterilizing protection of 2 of 6 pig-tailed monkeys, passively administered IgG purified from chimpanzees infected with the primary HIV-1 isolate, HIV-1DH12, and challenged intravenously with a SHIV bearing the identical envelope glycoprotein. In that experiment, the two completely protected animals were the recipients of the largest amount of chimpanzee IgG. In an extension of that study, much higher amounts of neutralizing IgG were administered to 15 pig-tailed macaques in order to obtain a statistically valid protective plasma neutralization endpoint titer. Using an in vitro assay, which measures complete neutralization of the challenge SHIV, we correlated the titers of plasma neutralizing antibodies at the time of virus inoculation (which ranged from 1:3 to 1:123) with the establishment of infection in virus challenged animals. Ten of 15 of these passively immunized monkeys were virus-free as monitored by: 1) DNA and RNA PCR analyses of PBMC and plasma, respectively; 2) virus isolation from lymph node specimens; and 3) transfer of whole blood plus suspensions of lymph node cells from protected, virus-challenged animals to naive macaques. An analysis of anti-SHIVDH12 neutralizing antibody levels in the plasma of the 21 monkeys in the two studies at the time of virus challenge indicated that the calculated neutralization titer capable of protecting 99% of macaques was 1:38.